Yersinia pestis is a Gram-negative coccobacillus causing the dangerous disease, plague. Survival of Y. pestis within host macrophages is important in the initial stages of infection. In our present work, DNA microarray was used to determine the expression profiles of Y. pestis strain 201 in response to in vitro simulating conditions of Mg(2+) limitation, polymyxin treatment and oxidative stress that could be found in phagolysosomal environment. It was demonstrated that Y. pestis made appropriate adaptive/protective responses to survive the stressful environments. There are the induced expression of antiphagocytic factors and Mg(2+) transporters under Mg(2+) limitation condition, the stimulation of drug/analogue sensitivity and glycerol assimilation after polymyxin treatment, and the differential expression in genes encoding stress-responsive proteins, components of cell envelope, iron assimilation and regulatory functions in response to both Mg(2+) limitation and polymyxin treatment. Under oxidative stress, Y. pestis uses several mechanisms, especially including the induced expression of detoxification enzymes and DNA repair proteins, to protect from or repair the oxidative cell damages. This microarray analysis would provide the candidates for identifying genes or pathways required for growth and proliferation of Y. pestis in macrophages.